Angiotensin II Upregulates Endothelial Lipase Expression via the NF-Kappa B and MAPK Signaling Pathways

Zhang, Xiaoli; Wu, Minghui; Jiang, Hong; Jiang, Hao; Zhang, Qingli; Zhu, Qing; Saren, Gaowa; Zhang, Yun; Meng, Xin; Yue, Xin

doi:10.1371/journal.pone.0107634

Cited by 27 publications

(18 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NF-κB has a key role in inflammatory and immune regulation and is found in a diversity of cells ( 30 ). Zhang et al ( 12 ) reported that PAE revokes colitis induced by dextran sulfate sodium through the Toll-like receptor 4-dependent pathway.…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

Zhang

Wang

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Paeoniflorin (PAE), a principal bioactive component of Paeonia lactiflora Pall., appears to have antitumor properties. However, the pharmacological activity of PAE in endometrial cancer and the specific mechanisms have remained largely elusive. The present study aimed to determine the antitumor activity of PAE in the human endometrial cancer cell line RL95-2 and explore the potential mechanisms. Cell proliferation was assessed to evaluate the antitumor effect of PAE towards RL95-2 cells via a Cell Counting Kit-8 assay. Protein expression was examined to investigate changes in the signaling pathways of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB in RL95-2 cells during PAE treatment by western blot analysis. The results revealed that PAE significantly and dose- and time-dependently inhibited the proliferation of RL95-2 cells. In addition, PAE activated MAPK signaling pathways (p38, JNK and ERK) and the NF-κB signaling pathway. Furthermore, p38 MAPK and NF-κB inhibitors (SB203580 and MG-132, respectively) prevented PAE-induced proliferative inhibition in RL95-2 cells. However, ERK and JNK inhibitors (PD98059 and BI-78D3, respectively) did not produce such an inhibition. In conclusion, the present study demonstrated that PAE exerts its anti-proliferative activity via activating p38 MAPK and NF-κB signaling pathways in endometrial cancer cells, providing a potential new drug of choice for endometrial cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

Zhang

Wang

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…Our previous results demonstrated that both NF-κB and c-Jun/AP-1 are involved in anti-β 2 GPI/β 2 GPI-induced TF expression in monocytes [ 17 ]. In the present study, we show for the first time that NF-κB and c-Jun/AP-1 are also involved in anti-β 2 GPI-induced expression of prothrombotic and proinflammatory molecules in vivo , and that these effects can be attenuated by PDTC (a specific inhibitor of NF-κB) [ 31 ] and Curcumin (a potent inhibitor of AP-1) [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of NF-κB and c-Jun/AP-1 on the Expression of Prothrombotic and Proinflammatory Molecules Induced by Anti-β2GPI in Mouse

Xia

Xie

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Our previous data demonstrated that nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are involved in the process of anti-β2GPI/β2GPI-induced tissue factor (TF) expression in monocytes. However, the role of NF-κB and AP-1 in pathogenic mechanisms of antiphospholipid syndrome (APS) in vivo has been rarely studied. This study aimed to investigate whether NF-κB and c-Jun/AP-1 are involved in anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in mouse. IgG-APS or anti-β2GPI antibodies were injected into BALB/c mice in the presence or absence of PDTC (a specific inhibitor of NF-κB) and Curcumin (a potent inhibitor of AP-1) treatment. Our data showed that both IgG-APS and anti-β2GPI could induce the activation of NF-κB and c-Jun/AP-1 in mouse peritoneal macrophages. The anti-β2GPI-induced TF activity in homogenates of carotid arteries and peritoneal macrophages from mice could significantly decrease after PDTC and/or Curcumin treatment, in which PDTC showed the strongest inhibitory effect, but combination of two inhibitors had no synergistic effect. Furthermore, anti-β2GPI-induced expression of TF, VCAM-1, ICAM-1 and E-selectin in the aorta and expression of TF, IL-1β, IL-6 and TNF-α in peritoneal macrophages of mice were also significantly attenuated by PDTC and/or Curcumin treatment. These results indicate that both NF-κB and c-Jun/AP-1 are involved in regulating anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in vivo. Inhibition of NF-κB and c-Jun/AP-1 pathways may be beneficial for the prevention and treatment of thrombosis and inflammation in patients with APS.

show abstract

“…AngII can modulate gene expression via the activation of multiple downstream signaling pathways, such as PI3K, NF-kB (p65), and MAPK, through AT1R or AT2R (24)(25)(26). To identify the signaling pathway by which AngII up-regulates the expression of AGGF1, we studied PD98059, SB203580, SP600125, and PDTC, which specifically inhibit the phosphorylation of ERK1/2, p38, JNK, and p65, respectively.…”

Section: Angii Up-regulates the Expression Of Aggf1 Via The Nf-kb Sigmentioning

confidence: 99%

Angiotensin II increases angiogenesis by NF‐κB–mediated transcriptional activation of angiogenic factor AGGF1

Xie²,

Deng³

et al. 2018

FASEB j.

View full text Add to dashboard Cite

Angiogenic factor with G-patch and FHA domains 1 (AGGF1) is involved in vascular development, angiogenesis, specification of hemangioblasts, and differentiation of veins. When mutated, however, it causes Klippel-Trenaunay syndrome, a vascular disorder. In this study, we show that angiotensin II (AngII)-the major effector of the renin-angiotensin system and one of the most important regulators of the cardiovascular system-induces the expression of AGGF1 through NF-κB, and that AGGF1 plays a key role in AngII-induced angiogenesis. AngII significantly up-regulated the levels of AGGF1 mRNA and protein in HUVECs at concentrations of 10-40 μg/ml but not >60 μg/ml. AngII type 1 receptor (AT1R) inhibitor losartan inhibited AngII-induced up-regulation of AGGF1, whereas AT2R inhibitor PD123319 further increased AngII-induced up-regulation of AGGF1. Up-regulation of AGGF1 by AngII was blocked by NF-κB inhibitors, and p65 binds directly to a binding site at the promoter/regulatory region of AGGF1 and transcriptionally activates AGGF1 expression. AngII-induced endothelial tube formation was blocked by small interfering RNAs (siRNAs) for RELA (RELA proto-oncogene, NF-κB subunit)/p65 or AGGF1, and the effect of RELA siRNA was rescued by AGGF1. AngII-induced angiogenesis from aortic rings was severely impaired in Aggf1 mice, and the effect was restored by AGGF1. These data suggest that AngII acts as a critical regulator of AGGF1 expression through NF-κB, and that AGGF1 plays a key role in AngII-induced angiogenesis.-Si, W., Xie, W., Deng, W., Xiao, Y., Karnik, S. S., Xu, C., Chen, Q., Wang, Q. K. Angiotensin II increases angiogenesis by NF-κB-mediated transcriptional activation of angiogenic factor AGGF1.

show abstract

Angiotensin II Upregulates Endothelial Lipase Expression via the NF-Kappa B and MAPK Signaling Pathways

Cited by 27 publications

References 49 publications

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF‑κB signaling pathways

The Effects of NF-κB and c-Jun/AP-1 on the Expression of Prothrombotic and Proinflammatory Molecules Induced by Anti-β2GPI in Mouse

Angiotensin II increases angiogenesis by NF‐κB–mediated transcriptional activation of angiogenic factor AGGF1

Contact Info

Product

Resources

About